The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

BACKGROUND: Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination. RESULTS: The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. CONCLUSIONS: The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model

Wideband DOA Estimation on Co-prime Array via Atomic Norm Minimization

This paper introduces a low complexity wideband direction-of-arrival (DOA) estimation algorithm on the co-prime array. To increase the number of the detectable signal sources and to prevent an unnecessary increase in complexity, the low dimensional co-prime array vector is constructed by arranging elements of the correlation matrix at every frequency bin. The atomic norm minimization (ANM)-based approach resolves the grid-mismatch, which causes an inevitable error in the compressive sensing (CS)-based DOA estimation. However, the complexity surges when the ANM is exploited to the wideband DOA estimation on the co-prime array. The surging complexity of the ANM-based wideband DOA estimation on the co-prime array is handled by solving the time-saving semidefinite programming (SDP) motivated by the ANM for multiple measurement vector (MMV) case. Simulation results show that the proposed algorithm has high accuracy and low complexity compared to compressive sensing (CS)-based wideband DOA estimation algorithms that exploit the co-prime array

Super-Resolution DoA Estimation on a Co-Prime Array via Positive Atomic Norm Minimization

A super-resolution direction-of-arrival (DoA) estimation algorithm that employs a co-prime array and positive atomic norm minimization (ANM) is proposed. To exploit larger array cardinality, the co-prime array vector is constructed by arranging elements of a correlation matrix. The positive ANM is a technique that can enhance resolution when the coefficients of the atoms are the positive real numbers. A novel optimization problem is proposed to ensure the coefficients of the atoms are the positive real numbers, and the positive ANM is employed after solving the optimization problem. The simulation results show that the proposed algorithm achieves high resolution and has lower complexity than the other ANM-based super-resolution DoA estimation algorithm

Off-Grid DoA Estimation via Two-Stage Cascaded Neural Network

This paper introduces an off-grid DoA estimation via two-stage cascaded network which can resolve a mismatch between true direction-of-arrival (DoA) and discrete angular grid. In the first-stage network, the initial DoAs are estimated with a convolutional neural network (CNN), where initial DoAs are mapped on the discrete angular grid. To deal with the mismatch between initially estimated DoAs and true DoAs, the second-stage network estimates a tuning vector which represents the difference between true DoAs and nearest discrete angles. By using tuning vector, the final DoAs are estimated by moving initially estimated DoAs as much as the difference between true DoAs and nearest discrete angles. The limitation on estimation accuracy induced by the discrete angular grid can be resolved with the proposed two-stage network so that the estimation accuracy can be further enhanced. Simulation results show that adding the second-stage network after the first-stage network helps improve the estimation accuracy by resolving mismatch induced by the discretized grid. In the aspect of the implementation of machine learning, results also show that using CNN and using PReLU as the activation function is the best option for accurate estimation

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

Background Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. Materials and methods HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7–8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. Bioluminescence imagings (BLIs) were performed before treatment and at 3, 7, and 14 days after treatment to measure the tumoral activities. The relative signal intensity (RSI) of each tumor was calculated by dividing the BLI signal at each time point by the value measured before treatment. At day 14 post-treatment, all tumor tissues were harvested to assess the apoptosis rates by pathological examination. Results The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. Conclusions The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model